The acquired immune deficiency syndrome (AIDS) is characterized by infection with multiple opportunistic pathogens which are normally removed from circulation and killed by the phagocytic cells of the reticuloendothelial system (RES). Since these infections are readily disseminated in patients with AIDS, we prospectively analyzed in vivo RES function by measuring Fc receptor clearance rates of anti-Rho IgG antibody sensitized, 51Cr labelled autologous erythrocytes in 15 patients with AIDS, 9 with AIDS related illnesses, 5 healthy homosexual men, 7 healthy heterosexual men, and 5 patients with mycobacterial infection but without AIDS. In addition, we have also started analyses of the in vivo clearance rates of C3b-coated erythrocytes in order to examine complement receptor clearance rates. Eleven of 15 AIDS patients (p 0.0005 vs controls) and 2 of 9 patients with AIDS related illness (p = NS vs controls) had prolonged Fc specific clearance rates when compared to healthy homosexual or heterosexual men. In contrast, patients with mycobacterial infections without AIDS had significantly more rapid clearance rates reflective of activated macrophage function. There was no association of clearance half times in AIDS patients with levels of circulating immune complexes, C3, C4, CH50, levels of T helper or T suppressor, or HLA phenotype. Likewise, C3b clearance rates were also markedly abnormal compared to healthy homosexual men and thus far there have been no correlation with any of the above immunologic parameters. However, defective clearance of both IgG and C3b coated red cells was correlated with prognosis: 6 of 11 patients with defective clearance rates died during the follow-up period as compared to 1 in 4 with normal clearance rates. One patient with AIDS who had a normal clearance rate had been receiving gamma interferon therapy. Data from this patient and from other in vitro studies suggests that gamma interferon may play an important role in altering macrophage activity in AIDS patients enabling them to resist disseminated opportunistic infections. In summary, the significance of this project is to provide in vivo evidence in AIDS of immunologic dysfunction of the reticuloendothelial system, a target organ frequently effected by opportunistic pathogens, and to provide evidence for the potential use of immunomodulators in the treatment of AIDS.